Because marihuana is such a widely used drug and there are some suggestions that prolonged use causes permanent alteration of the brain, it is imperative to more definitively determine whether the suggested persistent changes occur. The major aim of the proposed research is to clarify the issue involving the reported persisting neurotoxicity of marihuana. Disciplines involved in the proposed research include psychology, pharmacology, neurotoxicology, and neurophysiology. Macaque monkeys will be chronically exposed (5 days/week) to marihuana smoke or injected intravenously, on the same schedule, with Delta9-tetrahydrocannabinol. Behavioral and electrophysiologic parameters associated with performance of a cued reaction-time task and sensory-evoked response procedures sensitive to the effects of neurotoxicants will be used to evaluate acute and chronic effects of the drug. Following chronic exposure, additional tests of learning and of the integrity of the septal-hippocampal pathway will be utilized. By clarifying the issues discussed above, the mental health consequences of marihuana use will be better understood, thus providing more rational grounds on which to base medical and legal decisions concerning the drug.